Brandskyddet hos nya och gamla konstruktioner har blivit en väsentlig del av byggnadens säkerhet de senaste 70 åren. En av byggnadstyperna med högst skydd i form av brandskydd är sjukhus. I Sverige har sjukhus en generellt hög säkerhet, detta eftersom vissa personer har svårt att röra sig eller till och med är nedsövda. Även om dimensioneringen av dagens sjukhus utgår från ett högt brandskydd och säkerhetstänk, kan det finnas brister i det befintliga brandskyddet.   Examensarbetet syftar till att undersöka om luftslussens funktion avseende brandskydd mellan vårdavdelningar på sjukus och om de uppfyller den funktion som beskrivs i dagens regelverk. Detta kontrollerades genom att genomföra en litteraturstudie om varför och hur luftslussen har den funktion som den har idag. Det visar sig att under de senaste 25 åren har luftslussen i regelverken inte utvecklats. När bakgrundsinformationen var hämtad, genomfördes ett studiebesök på ett sjukhus där utrymningsövning med säng gjordes. Anledningen till detta var att beräkna medelhastighet för utrymning med säng och tid respektive dörr är öppen i luftslussen samt hur lång tid det tar att utrymma för att sedan återinträda till vårdnadssalen. Baserat på dessa tider gjordes sedan sex stycken databeräkningar med olika brandeffekter. Effekterna gjordes med och utan sprinkler samt med och utan luftsluss.   De sex CFD-beräkningarna delades in i tre fall. Det första fallet var en sängbrand med 800 kW som brandeffekt. Andra och tredje fallet illustrerade en 5 MW brand som effekt där ena fallet var med sprinkler och det andra utan. Varje fall bestod av två databeräkningar, ena beräkningen var med en luftsluss där dörrarna hade samma funktion som de hade på sjukhuset. Den andra var enbart med en dörr istället för luftsluss.   Utdatafilerna analyserades och jämfördes med varandra, först mot fallet med eller utan luftsluss och sedan mot de olika brandeffekterna. Detta gjordes för att se om någon brandgasspridning skedde beroende på om det var luftsluss eller ej och vid vilken brandeffekt samt tid brandgasspridning sker.   Resultaten visar att i alla databeräkningarna sker det brandgasspridning till intilliggande brandcell oavsett om det är luftsluss eller ej. Den enda modellen som luftslussen medför ett visst skydd mot brandgasspridning är vid sängbranden, men det är endast vid första passagen vilket ej kan anses uppfylla kravet.   Eftersom detta är en brist i de befintliga brandskyddsreglerna om hur ett sjukhus ska dimensioneras gällande luftslussarnas utformning, bör revideringar ske då brandgasspridning äger rum oavsett om det är luftsluss eller ej. För att personer ska känna sig säkra gällande skydd mot bränder bör ett bra brandskydd vara upprättat. Ett alternativ som används idag istället för luftsluss är att endast ha en brandklassad dörr, och sedan trycksätta intilliggande brandcell så ej brandgasen sprider sig. / For the past 70 years the safety protection of new and old construction has become very substantially, especially regarding fire protection. In form of fire protection, one of the most protective buildings is hospitals. In Sweden, hospitals has a generally high safe protection. People that are visiting the hospital could be visitors, victims or even anesthetized so the fire safety is important.   The purpose of this report is to investigate if the airlock functions at Swedish hospitals between different care sections fulfill the regulations. A literature study was made to understand why the regulations regarding airlocks at hospitals are formed the way they are. It resulted in that the regulations regarding airlocks haven’t been changed for the past 25 years. The report continued with a visit to a local hospital. An evacuation with hospital beds was made to gather information to the CFD calculations to know how the airlock doors was operating. The process was to start the evacuation based on a timer and stop the clock when the staff returned through the first door of the airlock and waited for the door to close.   A room was programmed in Pyrosim based on a real hospital section with an airlock that connected two rooms. The programming was based on the evacuation. Totally there were six CFD calculations with three different cases. Two different effects was used to illustrate the fire. A 800 kW hospital bed fire and two with the effect of 5 MW, one with sprinkler and the other without. The purpose of the data analysis was to investigate smoke movements and penetration within hospital facilities.   The data calculations showed that all 6 of the cases failed and smoke was penetrated through the airlock. Only one of the cases was able to withstand to 300 seconds and the other one failed at the first passage.   The results shows that there are a deficiency in the current regulation accordning the fire safety. An alternative that is used today when projecting a hospital, is to replace the airlock with a door and pressurize the room next door so that the smoke won’t spread as fast. Although pressurized rooms are used today, they need to be tested if they work. And if they do, be replacing the currently used airlocks.

Background: Supporting the public health care system is a priority for any advanced society. In line with who's recommendations, a key Law on The Protection of Health Against Harmful Effects of Addictive Substances was adopted in 2017, the main priority of which is to reduce passive smoking with its negative effects on humans. Objective: The aim of the study was to determine whether there was a change in tobacco use patterns and a change in smoking cessation incentives following the introduction of new legislative changes (Act No. 65/2017 Coll.). Methods: A prospective cohort study was carried out in connection with the introduction of Act No. 65/2017 Coll. Trained nurses were distributed in two waves, before the introduction of the law and three months after its introduction, prepared questionnaires were distributed to adult clients/patients addressed by general practitioners' offices in Prague. The condition was participation in both waves of the study. 131 completed adult questionnaires were submitted for subsequent processing. Changes in daily cigarette consumption, the ratio of cigarettes smoked in a restaurant, on the street, at home, and motivation to quit smoking were analysed. Results: A statistically significant reduction in daily cigarette consumption (on average 1.7 cigarettes per day)...

La fumée de cigarette peut endommager plusieurs organes de notre organisme, causant des maladies chroniques sévères et divers types de cancers. Elle interagit notamment avec les enzymes de métabolisme des médicaments de phase I et II, et contribue ainsi à la perturbation de la pharmacocinétique de divers médicaments chez les fumeurs. Les transporteurs membranaires sont des acteurs majeurs de l'absorption, la distribution et l'élimination de médicaments, et certains sont impliqués dans les interactions médicamenteuses. De plus, ils assurent le flux des molécules endogènes physiologiques vitales, et l'élimination de divers xénobiotiques toxiques non seulement chez les mammifères mais aussi chez les êtres unicellulaires, comme les levures. Ces transporteurs sont des cibles potentielles de la fumée de cigarette. D’où l'importance d'étudier l'interaction de la fumée de cigarette et de ses composés avec les transporteurs membranaires. Nos résultats démontrent que le condensat de fumée de cigarette (CSC) modifie l'activité fonctionnelle et/ou l'expression de plusieurs transporteurs hépatiques et rénaux in vitro dans des modèles cellulaires hépatiques et/ou non-hépatiques, notamment les OATPs (organic anion transporting polypeptide), l'OCT1 (organic cation transporter 1), la BCRP (breast cancer resistance protein) et l'OAT3 (organic anion transporter 3). Une implication remarquable du récepteur Ah (AhR) est mise en évidence dans la régulation de l'expression de certains transporteurs comme la MRP4 (multidrug resistance-associated protein), la BCRP, l'OAT2 et l'OCT1 dans des cellules HepaRG exposées au CSC. De plus, chez la levure Saccharomyces cerevisiae, le CSC inhibe l'activité d'efflux notamment des transporteurs de la rhodamine 123 et de la caféine, et induit, après trois heures, leur expression avec d'autres gènes qui sont aussi impliqués dans la résistance aux xénobiotiques comme les transporteurs de la membrane plasmique le Pdr5, le Snq2, le Pdr10, le Pdr15 et le Tpo1. Enfin, un effet inhibiteur remarquable des amines aromatiques hétérocycliques (AAH) est mis en évidence in vitro, notamment celui de Trp-P-1 et de Trp-P2 sur l'activité des transporteurs OCT1 et OCT2. De plus, les données in silico suggèrent que des descripteurs moléculaires des AAH comme l'AMW (average molecular weight), la qnmax (maximum negative charge) et le SPP (submolecular molarity parameter), sont des paramètres cruciaux de l'inhibition commune des OCT1, OCT2 et OCT3 par les AAH. Le CSC est donc un modulateur bifonctionnel, qui peut intervenir dans la régulation de l'activité et de l'expression des transporteurs membranaires hépatiques et rénaux, ainsi que ceux chez la levure. De telles interactions peuvent contribuer à l'altération de la pharmacocinétique des médicaments et des composés endogènes chez les fumeurs, d’où l'évaluation de l'exposition hépatique et rénale au CSC demeure indispensable. / Cigarette smoke can damage every part of our body, causing severe chronic diseases and various types of cancers. It also interacts with drug metabolizing enzymes of phase I and II, and thus contributes to pharmacokinetics disruption of various drugs in smokers. Membrane drug transporters are major actors involved in drugs absorption, distribution and elimination, and some are involved in drug-drug interactions. In addition, membrane drug transporters ensure the flow of vital physiological endogenous molecules, and the elimination of various toxic xenobiotics, not only in mammals but also in unicellular organisms, especially in yeasts. Therefore, this indicates the importance of studying the interaction of cigarette smoke and its contained chemicals with drug transporters. Our results demonstrate that cigarette smoke condensate (CSC) modifies the functional activity and / or expression of several hepatic and renal transporters in vitro in hepatic and / or non-hepatic cellular models, including OATPs (organic anion transporting polypeptide), OCT1 (organic cation transporter 1), BCRP (breast cancer resistance protein) and OAT3 (organic anion transporter 3). A remarkable implication of Ah receptor (AhR) was also demonstrated in MRP4 (multidrug resistance-associated protein), BCRP, OAT2 and OCT1 expression regulation in HepaRG cells exposed to CSC. In addition, in Saccharomyces cerevisiae, CSC inhibits the efflux activity of at least the rhodamine 123 and caffeine transporters, and induces, after three hours, their expression and that of others involved in xenobiotic resistance such as plasma membrane transporters Pdr5, Snq2, Pdr10, Pdr15 and Tpo1. Finally, a remarkable inhibitory effect of heterocyclic aromatic amines (HAA) is demonstrated in vitro, in particular that of Trp-P-1 and Trp-P-2 on the activity of OCT1 and OCT2. In addition, in silico data suggest that molecular descriptors of HAA such as AMW (average molecular weight), qnmax (maximum negative charge) and SPP (submolecular molarity parameter), may represent crucial parameters for common inhibition of OCT1, OCT2 and OCT3 transporters by HAA. Thus, CSC acts as bifunctional modulator, which can regulate activity and expression of hepatic and renal drug transporters as well as some membrane transporters in yeasts. Such interactions may contribute to the alteration of the pharmacokinetics of drugs and endogenous compounds in smokers, hence the evaluation of hepatic and renal exposure to CSC remains essential.

Background: Tobacco use exacerbates diseases, including tuberculosis (TB) and interferes with recovery from such outcomes. However, there is sparse research on the integration of tobacco cessation into TB programs. Moreover, there is limited evidence on how mHealth solutions for tobacco can enhance cessation among TB patients. This study aimed to assess the impact of a training program to integrate tobacco cessation in TB program on the knowledge of health workers. Methods: In June 2017, a 5-day training about tobacco use and control and the use of mHealth solutions to improve tobacco cessation and enhance adherence to TB treatment was conducted in Uganda. A comparison of percent of participants reporting knowledge on selected health outcomes of tobacco use and secondhand tobacco smoke (SHS) exposure was conducted. Knowledge was assessed on a 21-outcome-item before and after training. A non-parametric test, signrank for comparison of paired observations was conducted. The changes were considered statistically significant if the p-value was less than 5%. Results: Twenty three trainees from across the country attended (13 females, 10 males), with median age of the trainees was 39 years. Pre-training knowledge about tobacco use (66.6%) was higher than SHS exposure (45%). Following the training, both sets of knowledge significantly improved (median 100%). Pre-training knowledge about health effects of tobacco use was particularly low for diabetes (27%), meningitis (9.5%), ear infection (43%), impotence (47.6%), and fibrosis (30%). Except heart attack (76%), lung illness among children (91%), lung cancer (81%), and chronic lung disease (81%), pre-training knowledge about SHS was low for all other disease outcomes. Conclusions: Healthcare providers play critical role in preventing and reducing tobacco use. The low pre-training knowledge of the TB health workers suggests the critical need for training health providers in Uganda and elsewhere in Africa in order to curtail the increasing trend in usage.

京都大学 / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第17915号 / エネ博第287号 / 新制||エネ||60(附属図書館) / 30735 / 京都大学大学院エネルギー科学研究科エネルギー変換科学専攻 / (主査)教授 石山 拓二, 教授 星出 敏彦, 准教授 川那辺 洋 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DGAM

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Overall, the work presented in this thesis explored the impact of cigarette smoke on the immunopathogenesis of respiratory disease. This thesis highlighted the determinantal impact of cigarette smoke on (auto)antibody levels and pulmonary macrophage composition. Work completed by Steven P Cass 2016-2021. / Cigarette smoke is an insidious insult that is associated with a spectrum of respiratory diseases that range from cancer to obstructive diseases such as chronic obstructive pulmonary disease (COPD), to restrictive diseases such as idiopathic pulmonary fibrosis (IPF). In this thesis, we explore how cigarette smoke impacts immune components that contribute to respiratory disease. To begin, we assessed the impact of cigarette smoke on airway antibody and autoantibody levels. We assessed sputum, a non-invasive method to sample the lower airways, to directly assess the presence of antibodies and autoantibodies in COPD. Total immunoglobulin M (IgM), IgG and IgA were detectable in the sputum of subjects. Notably, in patients with mild to moderate COPD, current smoking status was associated with decreased IgM and IgG. Next, using a comprehensive autoantigen array, we measured matched sputum and serum autoantibodies in 224 individuals. Serum autoantibodies were more abundant than sputum autoantibodies and correlated strongly between two independent COPD cohorts. Overall, the autoantibody profile of a patient with COPD was the same as a control subject. A proportion of autoantibody specificities were differentially expressed in patients with COPD with anti-tissue autoantibodies weakly associated with measures of emphysema. Taken together, these data suggested chronic cigarette smoke exposure was associated with limited differential expression of autoantibodies, but these changes were not a reliable method to identify COPD status. In our third study, we assessed the impact of cigarette smoke exposure on the composition and function of pulmonary macrophage subpopulations. Macrophages perform a central role in respiratory host defence and are implicated in the pathobiology of several respiratory diseases. Using a mouse model of cigarette smoke exposure, we reported cigarette smoke-induced expansion of CD11b+ macrophage subpopulations including monocyte-derived alveolar macrophages and interstitial macrophages. The altered pulmonary macrophage composition following cigarette smoke exposure contributed to attenuated fibrogenesis in a model of bleomycin-induced lung injury. This study offered insight to pulmonary macrophage composition and function following cigarette smoke exposure. This thesis summarises the original contributions and work completed during the course of this Ph.D., aimed at understanding the impact of cigarette smoke exposure on immune components central to respiratory disease. In conclusion, these findings shed light on the presence of (auto)antibodies in patients with COPD and the composition of macrophage subpopulations following cigarette smoke exposure. / Thesis / Doctor of Philosophy (PhD) / Currently there are 1.3 billion people who use tobacco across the world. The most common method to consume tobacco is by smoking cigarettes. Cigarette smoking is well-known to cause disease; however, smoking rates are still increasing with more daily cigarette smokers in 2012 than there were in 1980. In this thesis, we explore the impact of cigarette smoke upon the immune system. We first assessed whether cigarette smoking impacts the levels of antibodies, proteins that are produced by the immune system to protect against foreign bodies, in healthy individuals, cigarette smokers without disease and patients with chronic obstructive pulmonary disease (COPD). We found that current smokers had decreased antibodies in the airways, thus predisposing cigarette smokers to increased damage. In our second study, we measured the presence of airway and blood autoantibodies. These are antibodies that target self and have the potential to inflict damage. We discovered that patients with COPD had minor changes in autoantibodies and these changes were weakly associated with emphysema. In our third study, we evaluated the impact of cigarette smoke on lung macrophages, cells that eat and destroy foreign bodies, in a mouse model of cigarette smoke exposure. Cigarette smoke increased the number of bone marrow-derived macrophages and this change in macrophage populations was associated with a reduced wound healing ability. Overall, these studies offer insight into how cigarette smoke impairs the function of the immune system and contributes to lung disease.

Type 2 diabetes and cigarette smoke exposure are associated with an increased risk of cardiovascular complications. The role of advanced glycation end-products (AGEs) is already well-established in numerous comorbidities including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with carboxy-methyl lysine-BSA, followed by mitochondrial respiration assessment. We found that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when co-treated with myriocin, an inhibitor of de novo ceramide biosynthesis. Moreover, we exposed WT and RAGE KO mice to side-stream cigarette smoke and found reduced mitochondrial respiration in the left ventricle myocardium from WT mice, but the RAGE KO mice were protected from this effect. Finally, conditional over-expression of RAGE in the lungs of mice also elicited a robust increase in left ventricular ceramides. Altogether, these findings suggest a RAGE-ceramide axis as an important contributor to cardiomyopathy.